COPD and Genetics: What Researchers Are Learning

Rest assured that researchers are working overtime to learn about COPD. This quest has lead them deep into the young and exciting field of genetics. Here is what they are learning about the link between COPD and genetics.

Asthma Genes Because asthma and COPD are complex diseases with many similar characteristics, researchers are investigating the possibility that both diseases are caused by some of the same genes. To learn the basics of genetic research, and the link between genetics and asthma, check out my post, Genetics and Asthma: A Brief Summary.

COPD Genes  When mutations (flaws, variations) occur on genes responsible for the development, maturation, and maintenance of substances responsible for keeping your lungs healthy, these are generally referred to as COPD genes. Such gene mutations or variations tell cells to do something abnormal that leads to the gradual loss of lung function over time due to loss of lung tissue (emphysema) and small airway obstruction (chronic bronchitis) 1. Since only some people have COPD genes, this should explain why only 10-15% of smokers develop COPD. This also points the finger at COPD, like asthma, being hereditary.

Heterogenous Each person with a susceptibility to developing COPD has a random assortment of COPD genes scattered along their genotype. This makes it so the disease presents itself differently from one person to the next. This should explain why some have it worse than others, and why what medicines work varies from one person to the next.

Active versus Inactive Almost all COPD genes are inactive when you are born, and only become activated due to chronic (day after day after day) exposure to environmental factors, such as chemicals in cigarette and wood smoke. COPD is the result of interactions between COPD genes and these environmental factors. 2,3

Gene Expression Each COPD gene plays a small role in the development of COPD. For instance, genes CHRNA3 and CHRNA 5 have been linked with emphysema, lung cancer, and nicotine addiction.4 If you have these COPD genes, they work together with your other COPD genes to cause the gradual loss of lung function over time. For this reason, most people do not present with observable symptoms until after the age of 40.

Phenotypes This is how your disease presents itself after your COPD genes interact with environmental factors.  It’s what determines what symptoms you will experience, how severe they will be, and how fast or slow your disease will progress over time. By focusing on specific phenotypes, researchers have an easier time searching for and identifying what genes are responsible for your specific phenotype. They can then study these genes to learn how to block their effects, thereby learning what medicines work or don’t work for each phenotype, thereby learning what medicines will best help you. Other terms used here are subtypes and subgroups. 5,6,7

COPD Phenotyping A trend among asthma researchers over the past several years has been to divide the disease into several phenotypes. So far, COPD is divided mainly into three phenotypes: emphysema predominant, airway predominant, or mixed. There have been other phenotypes created, such as cachexia and low exercise capacity, although they have not been well studied.1  As researchers learn more about our diseases, expect to hear more about COPD phenotyping and subtyping.

Precision Medicine In the coming years, you may even witness the creation of COPD guidelines tailored to each specific phenotype. This should help guide you and your physician to creating a treatment regimen specifically tailored to help you control your disease so you can breathe easy every day, and live a long productive life with it.

Protease-antiprotease theory Protease are enzymes responsible for the destruction of debris and dead lung tissue.  Anti-protease are responsible for inhibiting protease to prevent them from destroying healthy lung tissue. This theory postulates that COPD is the result of gene mutations that cause an excess of protease or a depletion of antiprotease. The end result is the gradual destruction of otherwise healthy lung tissue.8

SERINA1 This gene was discovered over 40 years ago, and, at the present time, is believed to be the only gene to cause COPD on its own, regardless of environmental exposure (meaning, even if you never smoked). It causes a depletion of the antiprotease Alpha 1-Antitrypsin, resulting in the development of emphysema, sometimes before the age of 40. It was basically by studying this gene that researchers came up with the protease-antiprotease theory. Researchers have since discovered a variety of genes that either cause an increase in protease, or a depletion of antiprotease. Although, unlike SERPINA1, all of these genes remain inactive unless they interact with environmental factors.

Matrix metalloprotease 12 (MMP12) This is an example of a gene responsible for protease that is probably activated by cigarette smoke. It’s responsible for elastase activity. Elastase is a protease enzyme that breaks up elastin, which helps lung tissue hold its shape. A flaw on this gene may cause an excess of elastin, which thereby destroys otherwise healthy lung tissue.8

Possible cure for COPD?  Researchers have learned that mice with a certain variation on MMP12 were immune to the effects of cigarette smoke. Efforts to mimic this effect on people without this variation may eventually lead to methods of preventing or curing emphysema. This is just one example of how genetic research should lead researchers to better treatment options and a possible cure.8

Tobacco smoke It contains oxidants that irritate airways. Perhaps by influencing COPD genes, this results in the release of proteases and an abundance of oxidants, resulting in oxidative stress. This results in an immune response leading to an increase in mucus production, inflammation, production of more proteases, and inhibition of antiproteases. So you can kind of get a picture of why cigarette smoking is a leading cause of COPD.8

Conclusion It may at times feel frustrating that so little is known about COPD. Keep in mind that this is not due to lack of effort on the part of researchers, it is due to the fact that the field of genetics is still very young, and our disease so very complex. The scope of what researchers know about genes and COPD genes in particular is far greater than what can possibly be expressed in a pithy post like this. However, we hope this gives you a better feeling of how hard people are working to help you breathe easier with COPD.


By providing your email address, you are agreeing to our privacy policy. We never sell or share your email address.

More on this topic

This article represents the opinions, thoughts, and experiences of the author; none of this content has been paid for by any advertiser. The team does not recommend or endorse any products or treatments discussed herein. Learn more about how we maintain editorial integrity here.

Join the conversation

or create an account to comment.